posted on 2025-04-15, 20:50authored bySeth D. Edwards, Zhen Tian, Young Jo Kim, Kyung Jae Jeong
Matrix metalloproteinases (MMPs) are a family of zinc-dependent
enzymes that degrade the extracellular matrix and play essential functions
in wound healing and tissue remodeling. However, the long-term overexpression
of MMPs is associated with a chronic wound environment. Treatments
that locally deactivate MMPs have been proposed to improve the outcomes
of nonhealing chronic wounds. In this Letter, sepia melanin, a natural
biopigment, is explored for the deactivation of MMPs, through chelation
of zinc ions. Melanins have chemical functional groups to bind to
various metal ions, which we demonstrate can be exploited for the
deactivation of MMPs. Melanin’s selectivity for zinc ions,
and ability to deactivate MMPs that are associated with chronic wounds
(MMP-1, MMP-2, and MMP-9) are examined, and its potential application
in wound healing is demonstrated by functional in vitro tissue assays,
mimicking the nonhealing wound environment. This is the first demonstration
of the use of melanin for MMP deactivation.